Tert-butyl acetoacetate → HCID 68647637, compound

HRID 1162515Notes

Reaction equation

HRID 1162515 reaction equation
[C:1]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH3:22][O:23][C:24](=[O:37])[CH2:25][C:26]1[CH:31]=[CH:30][C:29]([C:32](=[N:34]O)Cl)=[C:28]([Cl:36])[CH:27]=1>CCOCC.CC#N>[C:8]([O:7][C:1]([C:2]1[C:32]([C:29]2[CH:30]=[CH:31][C:26]([CH2:25][C:24]([O:23][CH3:22])=[O:37])=[CH:27][C:28]=2[Cl:36])=[N:34][O:4][C:3]=1[CH3:5])=[O:6])([CH3:11])([CH3:10])[CH3:9]

Participants

6

Reactant 3

HCID 15538Tert-butyl acetoacetateHCID 3251421Potassium bis(trimethylsilyl)amideHCID 72313573HCID 72313573, compound

Product 1

HCID 68647637HCID 68647637, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolvent2×

Procedure

tert-Butyl acetoacetate (5.0 g, 32 mmol) is dissolved in ether (100 mL). Potassium bis(trimethylsilyl)amide (5.7 g, 29 mmol) is added slowly while stirring at room temperature. Then the mixture is concentrated and triturated with hexane. The precipitate is filtered and dried to yield crude potassium enolate 23 (4.6 g, 23 mmol, 81%). Enolate 23 (1.0 g, 5.0 mmol) is dissolved in MeCN (50 mL) and cooled to 0° C. Intermediate 16 (1.1 g, 4.2 mmol) dissolved in MeCN (10 mL) is added dropwise and the solution is stirred at 0° C. for 2 hours. The solvent is evaporated and the remainder is purified by column chromatography using a hexanes/EtOAc gradient to afford 3-(2-chloro-4-methoxycarbonylmethyl-phenyl)-5-methyl-isoxazole-4-carboxylic acid tert-butyl ester 24 as a white solid: 1H-NMR (400 MHz, CDCl3) δ=7.41 (d, J=1.5 Hz, 1H), 7.33 (d, J=7.8 Hz, 1H), 7.25 (dd, J=8.0 Hz, J=1.5 Hz, 1H), 3.69 (s, 3H), 3.65 (s, 2H), 2.73 (s, 3H), 1.28 (s, 9H). MS calculated for C18H21ClNO5 (M+H+) 366.1, found 366.4.

Workup

  1. concentrationThen the mixture is concentrated
  2. customtriturated with hexane
  3. filtrationThe precipitate is filtered
  4. customdried
  5. customto yield crude potassium enolate 23 (4.6 g, 23 mmol, 81%)
  6. temperaturecooled to 0° C
  7. additionis added dropwise
  8. stirringthe solution is stirred at 0° C. for 2 hours
  9. customThe solvent is evaporated
  10. customthe remainder is purified by column chromatography

Sources & evidence

ORD record
ord-526424eab3814f0a905243a158321cf8
Source dataset
uspto-grants-2010_10
Patent number
US07820705B2

Reaction notes

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